The implication of Shh–Smo signaling in epilepsy and seizures has been indirectly addressed in previous studies showing that somatic mutations in Shh pathway genes in humans are associated with hypothalamic hamartoma and drug-resistant epilepsy (Hildebrand et al., 2016; Saitsu et al., 2016). The gene discussed is SHH; the disease is congenital hypothalamic hamartoma syndrome.